benzofurans and Carotid-Artery-Diseases

Topics: Adult; Benzofurans; Carotid Artery Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Evaluation; Female; Furans; Humans; Lateral Medullary Syndrome; Male; Middle Aged; Succinates; Vasodilator Agents

The aim of this study was to investigate the effect of 3-n-butylphthalide (NBP) on the apoptosis of nerve cells in vascular dementia (VaD) model rats caused by cerebral small vessel disease (CSVD), and to explore its regulatory mechanism.. The model of VaD was successfully established in rats by carotid artery ligation. All rats were randomly divided into three groups, including the sham operation group, model group and NBP group. The neurobehavioral score was used to verify whether the model was successfully established. The changes in learning and memory abilities of rats were detected via water maze experiment. The levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase-3 (Caspase-3) in the serum of rats was detected by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was adopted to detect the apoptosis of nerve cells in brain tissues of rats. Moreover, the protein levels of phosphorylated phosphatidylinositol-3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in brain tissues of rats were measured using Western blotting.. Compared with the sham operation group, the neurobehavioral score of rats increased significantly, whereas learning and memory abilities decreased markedly in the model group. The levels of Bax and Caspase-3 in rat serum were remarkably up-regulated, and the apoptosis rate of nerve cells in brain tissues of rats increased significantly in the model group as well. Meanwhile, the levels of phosphorylated PI3K and phosphorylated Akt were notably declined. Compared with the model group, the neurobehavioral score decreased markedly, while learning and memory abilities were remarkably improved in the NBP group. The levels of Bax and Caspase-3 in rat serum were significantly down-regulated, and the apoptosis rate of nerve cells in brain tissues of rats were reduced in the NBP group. Furthermore, the protein levels of phosphorylated PI3K and phosphorylated Akt were remarkably elevated in the NBP group.. NBP can improve the morphology of brain tissue cells and the learning and memory abilities, and inhibit the apoptosis of nerve cells in VaD model rats with CSVD. The possible underlying mechanism may be related to the activation of the PI3K/Akt signaling pathway.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Behavior, Animal; Benzofurans; Brain Chemistry; Carotid Artery Diseases; Caspase 3; Cerebral Small Vessel Diseases; Male; Maze Learning; Neurons; Neuroprotective Agents; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Rats; Rats, Sprague-Dawley; Signal Transduction